SUMMARY The overarching objective of our proposal is to bring noninvasive human brain imaging into the microscale (50-500 micron isotropic) resolution in order to create a tool for studies of neuronal circuitry and network organization in the human brain. Our breakthrough technology, MR Corticography (MRCoG), represents substantial advances over existing MRI approaches. MRCoG achieves dramatic gains in spatial and temporal resolutions by focusing several different types of coil arrays on the cerebral cortex of the live human brain. These optimized high-density receiver arrays with 128 coils also serve as a shim array and thereby obtain much higher quality imaging. High-performance magnetic field gradients will be combined with state-of-the-art pulse sequences to produce over 30-times acceleration in echo planar imaging. This will enable us to reach 0.4 mm resolution in fMRI studies of the entire cerebral cortex. This unprecedented spatial resolution in human fMRI is sufficient to identify functional activity at different depth in the cortex corresponding to different cortical layers. MRCoG will also be used to achieve 100-200 micron resolution susceptibility contrast images and this enables us to map intra-cortical axon connections and the cytoarchitecture of human cortex. With over 10 times higher resolution than current 7T scanners, MRCoG will overcome current scale limitations in imaging the function and structure of cortical layers and columns. The evaluation and refinement of MRCoG will entail using advanced computational models of brain circuitry, feedforward and feedback neuronal circuit models and computational models for decoding the brain using data from layer specific and column specific fMRI. Functional and structural MRI performed with MRCoG will generate new avenues to explore human brain circuitry at an order of magnitude higher spatial resolution, while importantly image the entire cortex rather than by current approaches (e.g. zoomed imaging) that measure only small areas of cortex. Many existing 7T MRI scanners will be able to incorporate MRCoG high-resolution technology; therefore, MRCoG can be rapidly disseminated to neuroscience research centers and used to advance medical discoveries. We will evaluate MRCoG ability to resolve currently unobservable cortex abnormalities in epilepsy and autism spectrum disorder (ASD) and to improve localization and mapping of abnormal circuitry in the brain.